Mohamed J. Saadh
1 
, Mareb Hamed Ahmed
2* , Rafid Jihad Albadr
3, Gaurav Sanghvi
4, R. Roopashree
5, Aditya Kashyap
6, A. Sabarivani
7, Zafar Aminov
8, Waam Mohammed Taher
9, Mariem Alwan
10, Mahmod Jasem Jawad
11, Ali M. Ali Al-Nuaimi
121 Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan
2 College of Dentistry, Alnoor University, Mosul, Iraq
3 Ahl al Bayt University, Karbala, Iraq
4 Marwadi University Research Center, Department of Microbiology, Faculty of Science, Marwadi University, Rajkot-360003, Gujarat, India
5 Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
6 Centre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, 140401, Punjab, India
7 Department of Biomedical, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India
8 Department of Public Health and Healthcare management, Samarkand State Medical University, Samarkand, Uzbekistan
9 College of Nursing, National University of Science and Technology, Dhi Qar, Iraq
10 Pharmacy College, Al-Farahidi University, Baghdad, Iraq
11 Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq
12 Gilgamesh Ahliya University, Baghdad, Iraq
Abstract
Introduction: The Varicella-zoster virus (VZV) causes varicella (chickenpox) and herpes zoster (shingles), posing significant global health challenges. Despite existing vaccines, gaps in coverage and efficacy persist, necessitating novel vaccine designs. This study aimed to develop a multi-epitope vaccine targeting VZV using immunoinformatics and structural bioinformatics approaches.
Methods: MHC-I and MHC-II binding epitopes from VZV proteins (glycoprotein E, glycoprotein B, tegument protein IE63) were predicted using IEDB tools, prioritizing conserved epitopes with high binding affinity. A chimeric construct was engineered with 18 epitopes, adjuvants (β-defensin 3), and cell-penetrating peptides (HIV TAT), linked with GPGPG/AAY spacers. Antigenicity (VaxiJen), allergenicity (AlgPred), physicochemical properties (ProtParam), and solubility (SOLpro) were assessed. Tertiary structure modeling (GalaxyWEB) and refinement (GalaxyRefine) were performed. Docking (PatchDock) and dynamics simulations (GROMACS, 100 ns) evaluated TLR2-vaccine binding stability. Immune response was simulated (C-ImmSim), and codon optimization (JCAT) ensured E. coli expression compatibility.
Results: Non-allergenic, antigenic (VaxiJen score: 0.52), stable (instability index: 30.20), and soluble (GRAVY: -0.548). Molecular weight: 34 kDa; pI: 9.65. RMSD (3.8 nm) and RMSF analyses confirmed complex stability. Free energy landscape revealed low-energy binding states (0.3–1.8 kcal/mol). Simulated results showed robust IgG/IgM production, Th1 cytokines (IFN-γ, IL-2), and memory cell activation. Epitopes covered 100% of populations in Europe/North America and > 77% in Africa/South Asia.
Conclusion: The multi-epitope vaccine demonstrated strong immunogenicity, structural stability, and broad population coverage. Computational validation supports its potential as a candidate for preventing VZV infections, pending experimental verification in the future.